Breast cancer is one of the most prevalent forms of cancer in women and one of the leading causes of cancer deaths in women. Mammography, or radiographic imaging of breast tissue, has proven to be an effective procedure for detecting and diagnosing early stage breast tumors. As currently performed, however, mammography does not detect all breast cancers. The ability of mammography to detect early stage tumors varies among women, depending on the characteristics of the breast tissue examined. Detection of breast lesions are particularly problematic in women with radiologically "dense" breasts, i.e., breast tissue exhibiting a dense parenchymal pattern upon mammography. The radiographic density of the breast tissue can obscure breast lesions, making detection more difficult and increasing the likelihood that the lesion will be overlooked. Such false negative mammograms result in delay in the diagnosis, and subsequent treatment, of breast cancer.
The problem of detecting lesions in radiologically dense breasts is not a minor one. Approximately 25-50% of women have been reported to have a dense parenchymal pattern upon mammography (see e.g., Threat, B., et al. (1980) Cancer 45:2550-2556; Jackson, V. P., et al. (1993) Radiology 188:297-301; van Gils, C. H., et al. (1995) Br. J Radiol. 68:1133-1135), although the prevalence of dense breasts decreases with age (e.g., to approximately 6% in women over 60, as reported Threat, B., et al., supra). An association between radiologic breast density and an increased risk for breast cancer has been reported in numerous clinical studies (see e.g., Wolfe, J. N. (1976) Cancer 37:2486-2492; Krook, P. M., et al. (1978) Cancer 41:1093-1097; Threat, B., et al., supra; Andersson, I., et al. (1981) Radiology 138:59-62; Saftlas, A. F. and Szklo, M. (1987) Epidemiol. Rev. 9:146.varies.174; Warner, E., et al. (1992) Cancer Det. Prevent. 16:67-72; Ma, L., et al. (1992) J. Natl. Cancer Inst. 84:781-785; Ciatto, S. and Zappa, M. (1993) Eur. J. Radiol. 17:122-125; Oza, A. M. and Boyd, N. F. (1993) Epidemiol. Rev. 15:196-208; Jenks, S. (1994) J. Natl. Cancer Inst. 86:578-580; Boyd, N. F., et al. (1995) J. Natl. Cancer Inst. 87:670675). The observed increased cancer risk associated with breast density has been attributed to a combination of 1) breast parenchymal patterns being an actual risk factor in the development of breast tumors and 2) "masking" of early stage tumors in dense breasts (see e.g., Egan, R. I. and Mosteller, R. C. (1977) Cancer 40:2087-2090; Saftlas, A. F. and Szklo, M., supra; Oza, A. M. and Boyd, N. F., supra). Because of the reported association between breast density and cancer incidence, women with dense breasts are recommended to have more frequent mammograms, which exposes these women to the additional risks associated with mammography itself.
Few solutions to the problem of imaging the radiographically dense breast have been proposed. Approaches to improve detection of breast lesions in dense breasts have focused on the development of alternative imaging modalities to mammography, such as ultrasonography, transillumination, thermography, computed tomography, magnetic resonance imaging, radionuclide imaging and digital mammography, which may provide better resolution of lesions in dense breasts (see e.g., Jackson, V. P., et al. (1993) Radiology 188:297-301; Braeuning, M. P., et al (1995) Breast Cancer Res. Treat. 35:31-38). Use of an alternative imaging procedure, however, likely would require large expenditures by health care providers for new equipment and personnel training, which may hinder widespread application of this approach. Additional strategies for improving the detection of lesions in dense breast tissue are still needed, especially strategies that can be used with traditional mammography.